P870: EFFICACY AND SAFETY OF ELRANATAMAB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN (BCMA)-DIRECTED THERAPIES: A POOLED ANALYSIS FROM MAGNETISMM STUDIES
Authors: Salomon Manier, Alexander Lesokhin, Mohamad Mohty, Ruben Niesvizky, Christopher Maisel, Bertrand Arnulf, Sarah M. Larson, Asya Nina Varshavsky-Yanovsky, Xavier Leleu, Lionel Karlin, David H. Vesole, Nizar J Bahlis, Carlos Fernandez de Larrea, Noopur Raje, Eric Leip, Sharon T. Sullivan, Mohamed Elmeliegy, Andrea Viqueira, Ajay Nooka
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Studies in the elranatamab MagnetisMM program (MM-1, NCT03269136; MM-3, NCT04649359; MM-9, NCT05014412) enrolled patients with relapsed/refractory multiple myeloma (RRMM) treated with prior BCMA-directed therapies. Aims: The efficacy and safety of elranatamab monotherapy in patients with RRMM and prior exposure to BCMA-directed therapy was evaluated in a pooled analysis. Methods: Eligible patients received at least 1 proteasome inhibitor, 1 immunomodulatory drug, 1 anti-CD38 antibody, and 1 BCMA-directed therapy (antibody drug conjugate [ADC] and/or CAR-T cells). Pooled analysis included patients in MM-1 (n=13) who received SC elranatamab 215−1000 µg/kg; MM-3 (n=64) and MM-9 (n=9) who received the RP2D, SC 76 mg QW. Efficacy endpoints were assessed by investigator per IMWG criteria. Treatment emergent adverse events (TEAEs) were graded by CTCAE (MM-1, v4.03; MM-3 & MM-9, v5.0); cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded by ASTCT criteria. Results include data up through ~10 mo after last patient initial dose in all pooled studies. Results: In total, 86 patients were included. Median age was 66.0 y (range, 40−84); 47.7% male. At baseline, 69.8% had an ECOG PS ≥1; 24.4% had high risk cytogenetics; 54.7% had extramedullary disease. Patients received a median of 7.0 (3−19) prior lines of therapy, including BCMA-directed ADC (67.4%) and/or CAR T-cells (41.9%), 9.3% received both. 96.5% and 54.7% of patients were triple-class and penta-drug refractory, respectively; among patients who received ADC and CAR-T cells respectively, 79.3% and 27.8% were refractory to ADC and CAR-T cells. After a median follow-up of 10.3 mo (0.3−32.3), median duration of treatment was 3.3 mo (0.03−30.4). At data cut-off, 24.4% of patients remained on treatment; most common reason for permanent treatment discontinuation was progressive disease (44.2%). Objective response rate (ORR) was 45.3% (95% CI 34.6−56.5), with complete response or better achieved in 17.4% of patients. ORR for patients with prior BCMA-directed ADC and CAR-T cells was 41.4% (95% CI 28.6−55.1) and 52.8% (95% CI 35.5−69.6), respectively. Among responders, median time to objective response was 1.9 mo (0.3−9.3). Median duration of response (DOR) was not reached by 10 mo; the DOR rate at 9 mo was 72.4% (95% CI 54.7−84.2). DOR rate (95% CI) for patients with prior BCMA-directed ADC and CAR-T cells were 67.3% (43.1−83.0) and 78.9% (53.2−91.5) at 9 mo, respectively. Median progression-free survival was 4.8 mo (95% CI 1.9−7.7), and median overall survival was not reached by 10 mo, with a rate of 60.1% (95% CI 48.9−69.6) at 9 mo. Most common (≥25% of patients) TEAEs were CRS (65.1% [G3 1.2%]), anemia (59.3% [G3/4, 46.5%]), neutropenia (44.2% [G3/4, 40.7%]), thrombocytopenia (40.7% [G3/4, 29.1%]), diarrhea (33.7% [G3/4, 0%], and lymphopenia (32.6% [G3/4, 30.2%]). ICANS was reported in 5.8% (G3, 2.3%) of patients. Summary/Conclusion In patients with RRMM and prior exposure to BCMA-directed therapies, elranatamab was efficacious and well tolerated; no new safety signals were observed vs the BCMA-naïve population. Results support treatment with elranatamab in patients with RRMM post BCMA-directed therapy. Keywords: Clinical trial, B-cell maturation antigen, Bispecific, Multiple myeloma